title: Treatment with SiMiaoFang, an anti-arthritis chinese herbal formula, inhibits cartilage matrix degradation in osteoarthritis rat model.
abstract: A Chinese herbal preparation, SiMiaoFang (SMF), has been used clinically for treating arthralgia by virtue of its anti-inflammatory and pain-relieving activities. However, no evidence base links SMF to anti-osteoarthritis (OA), particularly its link to inhibiting cartilage matrix degradation. In this study, we undertook a characterization of anti-OA activity of SMF using an in vivo rat model induced by anterior cruciate ligament transection and medial meniscus resection (ACLT+MMx) together with in vitro studies with chondrocytes for further molecular characterization. ACLT+MMx rats were treated with SMF at doses of 0.63, 1.25, and 2.5 grams/kg per day for 6 weeks. SMF treatments significantly inhibited cartilage matrix degradation, as indicated by increasing proteoglycan and collagen content, particularly type II collagen expression in articular cartilage, decreasing CTX-II (collagen type II degradation marker), and increasing CPII (collagen type II synthesis marker) in circulation. Moreover, SMF suppressed synovial inflammation and inhibited release of interleukin-1β (IL-1β) and tumor necrosis factor-α in serum. The levels of serum prostaglandin E₂ and nitric oxide productions were decreased via suppression of the production of cyclooxygenase-2 and inducible nitric oxide synthase, respectively. Importantly, SMF interfered with OA-augmented expression of matrix metalloproteinases (MMPs) -3 and -13 and aggrecanases (ADAMTS) -4 and -5, which are considered to be key enzymes in cartilage matrix degradation, and simultaneously augmented OA-reduced tissue inhibitors of metalloproteinases (TIMPs) -1 and -3 expression in the joints. The largest changes in these parameters were found at the highest dose. Meanwhile, SMF significantly decreased MMP-3 and -13 and increased TIMP-1 and -3 at mRNA and protein levels in IL-1β-induced chondrocytes. These findings provide the first evidence that SMF effectively treats OA by inhibiting cartilage matrix degradation.
authors.affiliation: 1 Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences , Beijing, China .
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.forename: Zhen-Li
authors.initials: ZL
authors.lastname: Liu
authors.forename: Li
authors.initials: L
authors.lastname: Lim
authors.forename: Wei-Heng
authors.initials: WH
authors.lastname: Chen
authors.forename: Na
authors.initials: N
authors.lastname: Lin
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism; D000071121:ADAMTS4 Protein; D000071116:ADAMTS5 Protein; D000818:Animals; D016118:Anterior Cruciate Ligament / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002356:Cartilage / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D019902:Chondrocytes / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D008592:Menisci, Tibial / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010003:Osteoarthritis / Q000188:drug therapy* / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000378:metabolism
chemical_list: D016207:Cytokines; D004365:Drugs, Chinese Herbal; D018836:Inflammation Mediators; D019715:Tissue Inhibitor of Metalloproteinase-1; D019717:Tissue Inhibitor of Metalloproteinase-3; D051722:ADAM Proteins; C571365:ADAMTS4 protein, rat; D000071116:ADAMTS5 Protein; C518696:Adamts5 protein, rat; D000071121:ADAMTS4 Protein